Imprinting of the IGF2 gene is controlled in part by the H19DMR (differentially methylated region) gene, which plays an important role in parent-of-origin-specific silencing of neighboring H19 and IGF2. There are ontogenetic shifts in IGF2 imprinting and IGF promoter usage that may influence IGF bioavailability in placental and fetal tissues at critical stages of development.(48,49) Loss of imprinting (LOI) of IGF2 is strongly associated with cell proliferation and in many cases with human malignancies, including some sarcomas. This evidence concerns the gene IGF1 and sarcoma.